Extracts from the bark of the Magnolia species, e.g., Magnolia grandiflora and Magnolia officinalis (Family Magnoliacee), have long been known to possess desirable medicinal and therapeutic properties. Extracts from Magnolia bark have been shown to have anti-anxiety, anti-inflammatory, anti-microbial, anti-oxidant, anti-platelet, and neurotrophic properties. A variety of traditional Japanese and Chinese herbal medicines are derived from Magnolia species and have long been used to treat anxiety and neurotic disorders. Such herbal formulas include Houpu Tang, Xiao Zhengai Tang, Ping Wei San and Shenmi Tang from China, and Hange-koboku-to and Sai-boku-to from Japan. These formulas are traditionally prepared from the bark of such species as Magnolia officinalis and Magnolia obovata. 
The two major active principles identified in Magnolia bark extracts are magnolol and honokiol, which are positional isomers. Honokiol is 3′5-diallyl-2,4′-biphenyldiol (CAS [35354-74-6]) and magnolol is 5,5′-diallyl-2,2′-biphenyldiol (CAS [528-43-8]), as shown below:

In recent research, these compounds have been purified from extracts and shown to have potent medicinal effects, including anti-proliferative, anti-inflammatory, anti-bacterial, anti-anxiety, chondroprotectieve, neurotrophic and neuroprotective effects. Honokiol, in particular, has been extensively studied as a potential treatment for cancer, heart disease, multiple sclerosis, arthritis and osteoporosis. Honokiol has also found use in consumer products such as toothpastes and mouthwashes, anti-aging creams and as a nutritional supplement. Research has shown that honokiol is a potent promoter of neurite growth and can increase the survival and development of neurons in primary cultures. Honokiol is also a potent anti-proliferative agent against SVR cells in culture, and can selectively inhibit the growth of primary human endothelial cells compared to fibroblasts. In vivo, honokiol has been shown to be highly effective against angiosarcoma in nude mice, showing both inhibition of angiogenesis and promotion of tumour apoptosis. Indeed, honokiol is being evaluated as an alternative cancer treatments that lacks the side effects of traditional chemotherapy agents.
In addition to honokiol's use as a potential therapeutic agent, honokiol is also in demand as a precursor to derivatives of honokiol which may also have potent biological or therapeutic properties. For example, both dihydrohonokiol and tetrahydrohonokiol are minor components of natural Magnolia extract which also display potent pharmaceutical properties. These compounds can be prepared synthetically by the single or double-reduction of the allyl groups of honokiol, respectively. For example, the following two isomeric dihydrohonokiols have been shown to have potent anxiolytic properties in animals:

Other honokiol derivatives being evaluated for biological activity include products in which one or both double bonds are converted to cyclopropane rings, epoxide rings, thirane rings or aziridine rings, or compounds in which one or both hydroxy groups are converted to alkyl ethers, trifluoromethyl ethers, alkyl phosphate esters or dichloroacetate esters. For example, honokiol diepoxide has been reported to have potent anti-proliferative effects and to be a potential treatment for cancer:

Like other natural products, the mass production of honokiol for use in the manufacture of pharmaceutical and consumer products, either directly as an intermediate, would not be cost-effective if based on extraction from natural sources. In addition, extraction from a natural source entails the very high risk that undesirable closely related chemical compounds will be present as impurities in the final product. Instead, commercial viability of honokiol-based products requires an efficient, low-cost, high-yield method of chemical synthesis. However, this goal is also difficult to achieve due to the formation of isomeric compounds that are difficult to separate from the desired compound, honokiol. For example, common synthetic methods produce, in addition to honokiol, the isomeric and difficult-to-separate by-product, isohonokiol:

Many published synthetic methods include other drawbacks, such as costly purification procedures, expensive starting materials, expensive chemical reagents, low overall yields, long reaction times, and toxic metal residues that are difficult to eliminate from the final product.
For example, Reddy et al., Tetrahedron Letters 55 (2014) 1049-1051, discloses a 6-step synthetic method starting from cyclohexane-1,4-dione monoethylene ketal that yields a 2:3 mixture of honokiol and isohonokiol, which are very difficult to separate positional isomers (12% overall yield of honokiol). In addition, the starting material is relatively expensive (greater than $1000/kg). Srinivas, et al., Tetrahedron Letters 55 (2014) 4295-4297, discloses a six-step method starting from 2-bromoanisole involving two palladium catalysed aryl coupling steps that produces honokiol in about 68% overall yield. Palladium catalysed reactions are undesirable because of the very high cost of palladium reagents (e.g., greater than $50,000/kg) and the difficulty of removing palladium impurities from the final product. Harada, et al., Tetrahedron Letters 55 (2014) 6001-6003, report a similar six-step method employing two palladium catalysed coupling steps and starting from 4-hydroxybenzeneboronic acid. The latter compound is both expensive (greater than $4000/kg) and prone to stability issues (which affects the efficiency of the reaction, the purification of intermediates and the storage of starting material). In addition, the use of two steps catalysed by expensive palladium reagents further makes the Harada method poorly suited to commercial use.
There is thus a need for an improved synthetic method for the production of honokiol which is high-yielding, efficient and cost-effective.